Recombinant DNA Advisory Committee - 12/3-4/92 
a single dose at the highest concentration. The investigators propose to perform HeLa 
cell assays in which lCr PFU will be plated onto 10 7 cells. 
Dr. Post said that there is no requirement that the virus should be handled under sterile 
conditions during the purification process. The investigators responded that they will use 
sterile filters in the preparation and perform sterility testing. Perhaps the reason that 
sterility is not as critical as for the other protocols is that the vector will be administered 
to the nasal epithelium. 
Dr. Post said that most of the pertinent issues have been dealt with effectively, and this 
protocol is complementary to the CF protocols reviewed earlier. He recommended that 
the protocol should be approved by the RAC. 
Review-Dr. Hirano 
Dr. Hirano expressed concern about the proposed sample size of the study. The 
investigators will treat a total of 3 patients, and each patient will receive a different 
vector dose, i.e., 2 x 10 6 , 2 x 10 7 , and 5 x 10 7 PFU. Will sufficient information be 
obtained to fulfill the stated objectives of this protocol; specifically, can safety and 
efficacy be demonstrated? What is the likelihood that patients will become ineligible for 
participation in future studies in which assessment of therapeutic benefits is a primary 
objective? What is the current status of the investigator's ability to produce production 
lots that have the required titer and absence of contaminating materials? 
Review-Dr. Carmen 
Dr. Carmen stated that he would like Dr. Welsh to discuss the implication of not 
incorporating the E3 deletion into the proposed vector. He noted that this protocol, 
along with the two CF protocols approved earlier, are important CF research being 
conducted at 3 separate universities focusing on the cutting edge of clinical investigation. 
This area of research needs as many qualified investigators working on therapies as 
possible. Dr. Carmen recommended approval of this protocol. 
Other Comments 
Ms. Meyers stated that the University of Iowa IRB expressed concern about the 
requirement that the patient will be held responsible for making arrangements for the 
payment of expenses related to treatment. Dr. Welsh's response states, I agree with you 
and your committee's concern that a policy may need to be instituted to support the payment 
of any injury that could be incurred in the absence of negligence , but the present wording 
and regulations are ones with which I must comply. Ms. Meyers asked Dr. Welsh to 
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Recombinant DNA Research, Volume 16 
